Disturbances in Colonic Physiology

Physiology of Constipation
Constipation refers to stools that are infrequent or hard to pass (or both). Arbitrary
definitions have been used. Individuals with constipation are an incredibly
heterogeneous group. Distinct subtypes of constipation occur and require different
treatment modalities, but even within these subtypes there can be wide variability
in the clinical presentation and pathophys- iologic etiology. There may be dietary,
pharmacologic, sys- temic, or local causes. Many people have constipation caused
by dietary and lifestyle neglect. Two primary functions of the colon, solidifying
chyme into stool and laxation, are interde- pendent on adequate dietary fiber.
Dietary fiber normalizes large bowel function.77,78 Recommendations for
adequate fiber intake ranges from 20 to 35 g per day for adults.79 Fiber is generally soluble or insoluble and seems to improve stool weight by different
mechanisms. Oat bran, which is soluble, seems to increase stool weight by
providing rapidly fermenting soluble fiber to the proximal colon. This allows for
bacterial growth which is sustained until excretion. It seems that the increase in
stool mass is from higher bacterial content and increased excretion of lipid and
fat.80 Insoluble fiber such as wheat bran increases stool weight by increasing
dietary fiber (undigested plant material) in the stool. Wheat bran also increases fat
excretion, but not to the extent of oat bran.80 Interestingly, fiber intake in the
United States is low. One explanation is that to achieve 15 g of fiber intake daily, 11
servings of refined grains and 5 servings of fruit and vegetables are needed for
individu- als consuming 15002000 kcal daily.77 Additionally, constipation may be
seen more frequently in sedentary people. In fact, abdominal cramps and diarrhea
are reported more frequently in runners.81,82 Acute graded exer- cise has been
shown to actually decrease phasic colonic motor activity. However, after the
exercise, there was an increase in the number and amplitude of propagated
pressure waves. It is believed that this post-exercise pattern may increase the propagating activity and propel stool.43 Idiopathic slow transit constipation involves a
measurable delayed movement of material through the colon. These patients are
not helped (in fact may be made worse) with increased dietary fiber. They seem to
have altered colonic motor response to eating and impaired or decreased HAPCs of
the colon.50,64 This leads to reduced or absent colonic propulsive activity.83,84
Abnormalities in the neuronal network are suspected and recently a pan-colonic
decrease in the ICC has been shown.56 As with other areas of colonic study, this
one also needs much more investigation.
Irritable bowel syndrome (IBS) can manifest with multiple forms. It usually is
characterized as altered bowel habits and pain directly related to the altered bowel
habits. In one form, constipation can be the predominant feature. This may encompass about 30% of the IBS population and traditionally over- whelmingly affects
women. This group of patients can show an overlap with those having slow transit
constipation, but may have a normal transit study.85 Pharmaceutical companies

have targeted drugs that affect metabolism of serotonin, which seems to be

involved in the regulation of motility, sensitivity, and intestinal secretions. The
specific 5-hydroxytryptamine (5-HT)4 receptor is involved in intrinsic sensory
reflexes within the gut. Tegaserod is a 5-HT486 agonist that has been approved by
the Food and Drug Administration (FDA) (July 2002) for treatment of this group of
patients.87 Additionally, cholecystokinin-1 antagonists are in trials for treatment of
patients with constipation-predominant IBS.87
Obstructed Defecation
Obstructed defecation usually results from abnormalities in pelvic function versus
colonic function. Typically this prob- lem is associated with failure of the puborectalis
to relax with defecation, rectocele, perineal descent, or other pelvic- and rectalassociated issues. Failure of the rectum to evacuate may lead to marker studies
which also show marker collection in the left colon.88 This may also be associated
with colonic total inertia.89 A colonic source, which is a variant in obstructed
defeca- tion, is a sigmoidocele. Although rare, the sigmoid is seen to migrate into
the pelvis with defecation and obstruct evacua- tion of stool. This form can be
relieved and treated with a sig- moid resection, but the clinician should be aware of
other pelvic floor abnormalities.
Ogilvies Syndrome
Ogilvies syndrome was described initially in 1948. It is also known as acute colonic
pseudoobstruction. The pathophysiol- ogy is not clearly understood. Based on
evidence from phar- macologic studies, it seems that Ogilvies original hypothesis is
as correct as the current facts; namely, there seems to be an imbalance of
autonomic innervation to the gut. The parasym- pathetic nerves, which are
responsible for stimulating gut motility, have decreased function or input and the
sympathetic nerves, which are inhibitory, increase their input.90 Because of the law
of Laplace, the cecum can be the site of extreme dilata- tion (it requires the
smallest amount of pressure to increase in size and therefore increase the wall
tension). Treatment has focused on ruling out a distal obstruction with a
Gastrografin enema and if needed colonoscopic decompression. However,
pharmacologic treatment with neostigmine has been success- ful.91 This drug is a
cholinesterase inhibitor that allows more available acetylcholine for
neurotransmission in the parasym- pathetic system (excitatory) to promote
contractility.92
28 T.L. Hull
Irritable Bowel Syndrome
As stated above, IBS is characterized by altered bowel habits associated with pain.
Besides the constipation-predominant type described above, there can be a
diarrhea-predominant type and a mixed type. The pathophysiology of IBS has

received extensive study, but it remains unclear. Abnormal motility, visceral

hypersensitivity, inflammation, abnormali- ties in extrinsic autonomic innervation,
abnormal braingut interaction, and the role of psychosocial factors have been
investigated. If IBS is found in men it tends to be more diar- rhea-predominant type.
Treatment is based on the nature and severity of symptoms. Education,
reassurance, and dietary modification (elimination of foods that aggravate the problem) are the first steps. For those who do not respond, med- ication is considered.
Antispasmodics (anticholinergic) medication is considered for those with pain and
bloating that is especially aggravated by meals. Usually, antispasmodics and
anticholinergic agents are considered on an as-needed basis. Low-dose tricyclic
antidepressants may be considered when the pain is more constant and perhaps
disabling.86 Considering specific types, no good pharmacologic research is available
for the mixed-type IBS patients. However, for the diarrhea prone, 5-HT3 antagonists
have been found to be effective. Alosetron was initially FDA approved (March 2000)
only to be withdrawn after some patients suffered ischemic colitis and even
death.87 In June 2002, it was reapproved with restrictions that require the prescriber to demonstrate educational understanding regarding the drug. Additional
drugs are also undergoing trials.